TYPE IV HYPERSENSITIVITY REACTION

Type IV - Hypersensitivity
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Type IV hypersensitivity which can also be called delayed-type hypersensitivity (DTH) reaction is a cell-mediated allergic reaction that induces a localized inflammatory reaction through the release of cytokines. In delayed-type hypersensitivity, sensitized T lymphocytes mediate the release of cytokines (e.g., interleukins and interferons) that recruit macrophages to the site of infection or allergen administration. The recruited and activated macrophages release lytic enzymes that cause localized tissue damage at the affected body site as well as contain the activities of the invading allergen. Sensitized T lymphocytes (particularly TDTH cells) are the main effector molecules of the type IV hypersensitivity reaction. Macrophages also act as effector cells of DTH response. Immunoglobulins and complements play no roles in delayed-type hypersensitivity reaction as is obtainable in Type I, II and III hypersensitivity reactions. Unlike other forms of hypersensitivity reactions (inclusive of Type I, II and III reactions as aforementioned) that are immediate-type allergic reactions and occur soon after the injection of the allergen into the host; the type IV hypersensitivity reaction occurs hours or days after the allergen or antigen have invaded the animal or human host and thus the name, delayed-type hypersensitivity (DTH) reaction.

There are plethora of pathogenic microorganisms and other substances that induce a delayed-type hypersensitivity reaction. These microbes and substances that causes DTH reaction in humans include: intracellular bacteria (e.g., Mycobacterium tuberculosis, Brucella abortus, Listeria monocytogenes and M. leprae), intracellular viruses (e.g., measles virus, herpes simplex virus and small pox virus or variola), intracellular protozoa (e.g., Leishmania species), intracellular fungi (e.g., Candida albicans, Cryptococcus neoformans, and Histoplasma capsulatum), and other contact allergens such as poison ivy and poison oak that causes several skin reactions in sensitized humans. Delayed-type hypersensitivity (DTH) unlike other forms of hypersensitivity reactions has several protective roles in the animal or human host aside causing localized tissue damage. For example, type IV hypersensitivity defends the host against intracellular microorganisms and other contact allergens.

The recruitment and activation of macrophages in the type IV hypersensitivity reaction to the site of infection is critical in defending the body against intracellular microorganisms which are known to live inside the host cell and away from possible attack by antibodies and other components of the host’s immune system. The intracellular pathogen is eliminated with little damage to the host cell but if the allergen or antigen is not easily removed, an extensive DTH reaction may result in adverse inflammatory reaction that is characteristic of type IV hypersensitivity reaction. Contact dermatitis caused by direct body contact with some plants or flowers (e.g., poison ivy and poison oak tree) is a typical example of delayed-type hypersensitivity reaction. In the hospital, skin testing (e.g., Mantouxtest) based on DTH response is used to determine the sensitivity or sensitization of a person’s immune system to the invasion of an allergen or antigen (in this case: exposure to the tubercle bacilli, Mycobacterium tuberculosis – that causes tuberculosis, TB).

Further reading

William E.P (2003). Fundamental Immunology. 5th edition. Lippincott Williams and Wilkins Publishers, USA.

Stevens, Christine Dorresteyn (2010). Clinical immunology and serology. Third edition. F.A. Davis Company, Philadelphia.

Silverstein A.M (1999). The history of immunology. In Paul, WE (ed): Fundamental Immunology, 4th edition. Lippincott Williams and Wilkins, Philadelphia, USA.

Paul W.E (2014). Fundamental Immunology. Seventh edition. Lippincott Williams and Wilkins, USA.

Male D, Brostoff J, Roth D.B and Roitt I (2014). Immunology. Eight edition. Elsevier Saunders, USA.

Levinson W (2010). Review of Medical Microbiology and Immunology. Twelfth edition. The McGraw-Hill Companies, USA.

Berzofsky J.A and Berkower J.J (1999). Immunogenicity and antigen structure. In Fundamental Immunology, 4th edition., W.E. Paul, ed., Lippincott-Raven, Philadelphia. 

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